EP3390343B1 - Resorcinol derivatives for cosmetic use thereof - Google Patents

Resorcinol derivatives for cosmetic use thereof Download PDF

Info

Publication number
EP3390343B1
EP3390343B1 EP16815770.9A EP16815770A EP3390343B1 EP 3390343 B1 EP3390343 B1 EP 3390343B1 EP 16815770 A EP16815770 A EP 16815770A EP 3390343 B1 EP3390343 B1 EP 3390343B1
Authority
EP
European Patent Office
Prior art keywords
radical
linear
denotes
alkyl radical
formula
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
EP16815770.9A
Other languages
German (de)
French (fr)
Other versions
EP3390343A1 (en
Inventor
Xavier Marat
Amélie GUEGUINIAT
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
LOreal SA
Original Assignee
LOreal SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by LOreal SA filed Critical LOreal SA
Publication of EP3390343A1 publication Critical patent/EP3390343A1/en
Application granted granted Critical
Publication of EP3390343B1 publication Critical patent/EP3390343B1/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
    • C07C39/02—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring monocyclic with no unsaturation outside the aromatic ring
    • C07C39/11—Alkylated hydroxy benzenes containing also acyclically bound hydroxy groups, e.g. saligenol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/347—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/37—Esters of carboxylic acids
    • A61K8/375—Esters of carboxylic acids the alcohol moiety containing more than one hydroxy group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
    • C07C69/12—Acetic acid esters
    • C07C69/18—Acetic acid esters of trihydroxylic compounds

Definitions

  • the present invention relates to the cosmetic use of compounds derived from resorcinol for depigmenting and / or whitening the skin, as well as certain novel compounds derived from resorcinol.
  • spots appear on the skin and more especially on the hands and face, conferring heterogeneity on the skin. These spots are due in particular to a high concentration of melanin in the keratinocytes located on the surface of the skin.
  • the mechanism of the formation of skin pigmentation that is to say the formation of melanin, is particularly complex and schematically involves the following main steps: Tyrosine ⁇ Dopa ⁇ Dopaquinone ⁇ Dopachrome ⁇ Melanin
  • Tyrosinase (monophenol dihydroxyl phenylalanine: oxygen oxidoreductase EC 1.14.18.1) is the essential enzyme involved in this series of reactions. It catalyzes in particular the reaction of transformation of tyrosine into Dopa (dihydroxyphenylalanine) thanks to its hydroxylase activity and the reaction of transformation of Dopa into dopaquinone thanks to its oxidase activity. This tyrosinase acts only when it is in the state of maturation under the action of certain biological factors.
  • a substance is recognized as depigmenting if it acts directly on the vitality of the epidermal melanocytes where melanogenesis takes place, and / or if it interferes with one of the steps in the biosynthesis of melanin either by inhibiting one of the enzymes involved in melanogenesis, or by intercalating itself as a structural analogue of one of the chemical compounds of the melanin synthesis chain, a chain which can then be blocked and thus ensure depigmentation.
  • Arbutin and kojic acid are known as skin depigmenting agents.
  • the subject of the invention is compounds of formula (I) as defined below for their dermatological use for depigmenting the skin.
  • a subject of the invention is also new compounds of formula (II) as defined below.
  • a subject of the invention is also a method of non-therapeutic cosmetic treatment for depigmentation, lightening and / or bleaching of keratin materials, in particular of the skin, comprising the application to the skin of at least one compound of formula ( I) as defined below.
  • a subject of the invention is also a composition comprising, in a physiologically acceptable medium, at least one compound of formula (II) as defined below.
  • a subject of the invention is also a non-therapeutic cosmetic process for depigmentation, lightening and / or bleaching of keratin materials, in particular of the skin, comprising the application of the composition described above.
  • this is the method for depigmenting, lightening and / or whitening the skin.
  • the invention also relates to the non-therapeutic cosmetic use of at least one compound of formula (I) as defined below as an agent for whitening, lightening and / or depigmenting keratin materials, in particular the skin.
  • the compounds in accordance with the invention make it possible to effectively depigment and / or lighten, or even whiten, the skin of human beings. humans. They are intended in particular to be applied to the skin of individuals exhibiting brownish pigmentation spots, spots of senescence, or to the skin of individuals wishing to combat the appearance of a brownish color originating from melanogenesis.
  • R 1 and R 2 are identical.
  • R 4 denotes H or a linear C 1 -C 4 alkyl radical, a branched C 3 -C 4 alkyl radical or a COR 5 radical, more preferably H or a COR 5 radical.
  • salts of the compounds of formula (I) as defined below comprise the conventional non-toxic salts of said compounds such as those formed from acid or base.
  • salts of amino acids such as, for example, lysine, arginine, guanidine, glutamic acid or aspartic acid.
  • the salts of the compounds of formula (I) can be chosen from alkali or alkaline earth salts such as sodium, potassium, calcium, magnesium; ammonium salts.
  • Acceptable solvates of the compounds described in the present invention include conventional solvates such as those formed during the preparation of said compounds due to the presence of solvents.
  • solvates due to the presence of water or of linear or branched alcohols such as ethanol or isopropanol.
  • optical isomers are in particular the enantiomers and the diastereoismers.
  • a “(C x -C y ) alkyl group” denotes a linear and saturated alkyl group comprising from x to y carbon atoms.
  • the saturated or branched linear alkyl groups can be chosen from: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl.
  • the particularly preferred compounds of formula (I) are chosen from: Structure Compound No. Chemical name 1 4- (3-Hydroxy-1-methyl-propyl) -benzene-1,3-diol 2 4- [4- (acetyloxy) butan-2-yl] benzene-1,3-diyl diacetate 3 3- (2,4-dihydroxyphenyl) butyl acetate as well as their salts, their solvates and their optical isomers, their racemates, alone or as a mixture.
  • the compounds of formula (I) are new and constitute another subject of the invention, as well as the compositions, in particular the cosmetic compositions, which contain them;
  • Resorcin A can react in the presence of a beta keto-ester B to lead to coumarin C.
  • the latter is reduced by catalytic hydrogenation according to conditions known to those skilled in the art to lead to D.
  • D can also be obtained from resorcinol A in the presence of an alpha beta unsaturated ester E.
  • the lactonic function of D is then reduced by hydrides, after possible prior modifications of the phenolic functions by known reactions of the those skilled in the art such as protection / deprotection reactions.
  • Obtaining the C and D derivatives via the reaction between (A and B) or (A and E) can be carried out in particular in the presence of an organic solvent which can be chosen from toluene, tetrahydrofuran, heptane, isooctane, methyltetrahydrofuran, methyl ethyl ketone, methyl isobutyl ketone, dioxane, ethyl acetate, isopropyl acetate, isododecane and their mixtures, in particular at a temperature between 15 and 200 ° C, optionally in the presence of a catalyst (acidic or basic) as described in the publications: Synthesis of 7-hydroxycoumarins by Pechmann reaction using Nafion resin / silica nanocomposites as catalysts: Laufer MC, Hausmann H, Hölderich WF, J of catalysis, 2003, 218, 315-320 ; Synthesis of 7-hydroxycoumarins catalysed by solid
  • the compounds of formula (I) for which R 1 and or R 2 denote a COR 5 group can be obtained by acetylation / esterification.
  • the acetylation / esterification reaction can be carried out with acetic anhydride when R 5 denotes a methyl radical (or more generally an R 5 COOCOR 5 anhydride) or acetyl chloride when R 5 denotes a methyl radical (or more generally an acid chloride R5COCl), especially in the presence of an aprotic solvent such as toluene, pyridine, tetrahydrofuran.
  • the acetylation / esterification reaction can be selective by employing protective groups on the functions which must not be acetylated / esterified and by carrying out, after acetylation / esterification, a deprotection reaction, according to known techniques of organic synthesis.
  • the reduction reaction of lactone D with hydrides to lead to derivative G can optionally be carried out in the presence of an aprotic organic solvent, in particular tetrahydrofuran, dioxane, dimethylformamide, dimethylsulfoxide, 2-methyltetrahydrofuran, dichloromethane, toluene, at a temperature between 0 ° C and 200 ° C, especially between 20 ° C and 60 ° C.
  • an aprotic organic solvent in particular tetrahydrofuran, dioxane, dimethylformamide, dimethylsulfoxide, 2-methyltetrahydrofuran, dichloromethane, toluene
  • the compounds of formula (I) according to the invention find very particular application in the cosmetics field.
  • composition according to the invention comprises, in a physiologically acceptable medium, a compound of formula (I) as described above.
  • physiologically acceptable medium By physiologically acceptable medium, one understands a medium compatible with the keratinous substances of human beings such as the skin of the body or of the face, the lips, the mucous membranes, the eyelashes, the nails, the scalp and / or the hair.
  • the compound (I) can be present in the composition according to the invention in an amount which can be between 0.01 and 10% by weight, preferably between 0.1 to 5% by weight, in particular from 0.5 to 3% by weight, relative to the total weight of the composition.
  • composition according to the invention is advantageously a cosmetic composition: it can comprise adjuvants usually used in the cosmetic field.
  • Mention may in particular be made of water; organic solvents, in particular C2-C6 alcohols; oils, in particular hydrocarbon-based oils, silicone oils; waxes, pigments, fillers, dyes, surfactants, emulsifiers; cosmetic active ingredients, UV filters, polymers, thickeners, preservatives, perfumes, bactericides, ceramides, odor absorbers, antioxidants.
  • organic solvents in particular C2-C6 alcohols
  • oils in particular hydrocarbon-based oils, silicone oils
  • waxes pigments, fillers, dyes, surfactants, emulsifiers
  • cosmetic active ingredients UV filters, polymers, thickeners, preservatives, perfumes, bactericides, ceramides, odor absorbers, antioxidants.
  • optional cosmetic adjuvants can be present in the composition in an amount of 0.001 to 80% by weight, in particular 0.1 to 40% by weight, relative to the total weight of the composition.
  • these adjuvants, as well as their proportions, will be chosen by a person skilled in the art such that the advantageous properties of the compounds according to the invention are not, or not substantially, altered by the addition envisaged.
  • compositions according to the invention at least one compound chosen from: desquamating agents; soothing agents, organic or inorganic photoprotective agents, moisturizing agents; depigmenting agents; anti-glycation agents; NO-synthase inhibitors; agents stimulating the synthesis of dermal or epidermal macromolecules and / or preventing their degradation; agents stimulating the proliferation of fibroblasts and / or keratinocytes or stimulating the differentiation of keratinocytes; muscle relaxants and / or dermo-relaxants; tensioning agents; anti-pollution and / or anti-radical agents; agents acting on the microcirculation; agents acting on the energy metabolism of cells; and their mixtures.
  • desquamating agents desquamating agents
  • soothing agents organic or inorganic photoprotective agents, moisturizing agents
  • depigmenting agents anti-glycation agents
  • NO-synthase inhibitors agents stimulating the synthesis of dermal or epidermal macromolecules and / or preventing their
  • composition according to the invention can be provided in all the galenic forms normally used in the cosmetics field, and in particular in the form of an aqueous or hydroalcoholic solution, optionally gelled, of an optionally two-phase lotion-type dispersion, of an emulsion.
  • compositions are prepared according to the usual methods. prefers to use according to this invention a composition in the form of an emulsion in particular oil-in-water.
  • the composition according to the invention can constitute a skin care composition, and in particular a cream for cleaning, protecting, treating or caring for the face, for the hands, for the feet, for the large anatomical folds or for the body (eg day creams, night creams, makeup removing creams, foundation creams, sunscreen creams); a fluid foundation, a cleansing milk, a protective or care body milk, an anti-sun milk; a skin care lotion, gel or foam, such as a cleansing lotion.]
  • reaction medium was cooled to 0 ° C. and 20 ml of water and then 250 ml of 1N HCl were carefully added.
  • the THF was evaporated off, then the residue was extracted 3 times with diethyl ether.
  • the combined organic phases were washed with saturated NaCl solution, then dried with Na2SO4, filtered and evaporated.
  • normal human melanocytes are cultured and distributed in 384 wells. After 24 hours, the culture medium was replaced by a medium containing compounds of formula (I) to be evaluated. The cells were incubated 72 hours before the measurement of the final optical density which measures the amount of melanin produced by melanocytes. A dose effect is implemented by using a wide range of concentrations of the compounds evaluated. Thus, by matching the concentrations and measurements of melanin, it is possible to determine an IC50 in ⁇ M: concentration at which 50% reduction in melanin synthesis is reached.
  • the value of the IC50 is 23.4 ⁇ M maximum concentration tested 200 ⁇ M.
  • the compounds of the invention have an activity on the reduction of melanogenesis much greater than that of compound (A) outside the invention;
  • a depigmenting composition for the skin comprising (in grams): Compound # 1 2 g PEG400 68 g Ethanol 30 g
  • composition applied to the skin helps to reduce dark spots.
  • a depigmenting gel for the skin comprising (% by weight): Compound # 2 0.25% Carbomer (Carbopol 981 from Lubrizol) 1% conservative qs water qsp 100%
  • composition applied to the skin helps to reduce dark spots.
  • Example 7 Demonstration of the depigmenting activity on a reconstructed pigmented epidermis
  • the melanin was quantified by analysis of images on histological sections after revelation by Fontana Masson staining. Each colored epidermis is photographed along its entire length using a camera connected to a microscope.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Emergency Medicine (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Cosmetics (AREA)

Description

La présente invention concerne l'utilisation cosmétique de composés dérivés de résorcinol pour dépigmenter et/ou blanchir la peau, ainsi que certains composés dérivés de résorcinol nouveaux.The present invention relates to the cosmetic use of compounds derived from resorcinol for depigmenting and / or whitening the skin, as well as certain novel compounds derived from resorcinol.

A différentes périodes de leur vie, certaines personnes voient apparaître sur la peau et plus spécialement sur les mains et le visage, des taches plus foncées et/ou plus colorées, conférant à la peau une hétérogénéité. Ces taches sont dues notamment à une concentration importante de mélanine dans les kératinocytes situés à la surface de la peau.At different periods of their life, some people see darker and / or more colored spots appear on the skin and more especially on the hands and face, conferring heterogeneity on the skin. These spots are due in particular to a high concentration of melanin in the keratinocytes located on the surface of the skin.

L'utilisation de substances dépigmentantes topiques inoffensives présentant une bonne efficacité est toute particulièrement recherchée en vue de traiter les taches pigmentaires.The use of harmless topical depigmenting substances exhibiting good efficacy is very particularly sought after with a view to treating pigment spots.

Le mécanisme de formation de la pigmentation de la peau, c'est-à-dire de la formation de la mélanine est particulièrement complexe et fait intervenir schématiquement les principales étapes suivantes :
Tyrosine → Dopa → Dopaquinone → Dopachrome → MélanineThe mechanism of the formation of skin pigmentation, that is to say the formation of melanin, is particularly complex and schematically involves the following main steps:
Tyrosine → Dopa → Dopaquinone → Dopachrome → Melanin

La tyrosinase (monophénol dihydroxyl phénylalanine: oxygen oxydo-reductase EC 1.14.18.1) est l'enzyme essentielle intervenant dans cette suite de réactions. Elle catalyse notamment la réaction de transformation de la tyrosine en Dopa (dihydroxyphénylalanine) grâce à son activité hydroxylase et la réaction de transformation de la Dopa en dopaquinone grâce à son activité oxydase. Cette tyrosinase n'agit que lorsqu'elle est à l'état de maturation sous l'action de certains facteurs biologiques.Tyrosinase (monophenol dihydroxyl phenylalanine: oxygen oxidoreductase EC 1.14.18.1) is the essential enzyme involved in this series of reactions. It catalyzes in particular the reaction of transformation of tyrosine into Dopa (dihydroxyphenylalanine) thanks to its hydroxylase activity and the reaction of transformation of Dopa into dopaquinone thanks to its oxidase activity. This tyrosinase acts only when it is in the state of maturation under the action of certain biological factors.

Une substance est reconnue comme dépigmentante si elle agit directement sur la vitalité des mélanocytes épidermiques où se déroule la mélanogénèse, et/ou si elle interfère avec une des étapes de la biosynthèse de la mélanine soit en inhibant une des enzymes impliquées dans la mélanogénèse, soit en s'intercalant comme analogue structural d'un des composés chimiques de la chaîne de synthèse de la mélanine, chaîne qui peut alors être bloquée et ainsi assurer la dépigmentation.A substance is recognized as depigmenting if it acts directly on the vitality of the epidermal melanocytes where melanogenesis takes place, and / or if it interferes with one of the steps in the biosynthesis of melanin either by inhibiting one of the enzymes involved in melanogenesis, or by intercalating itself as a structural analogue of one of the chemical compounds of the melanin synthesis chain, a chain which can then be blocked and thus ensure depigmentation.

L'arbutine et l'acide kojique sont connus comme agents dépigmentants de la peau.Arbutin and kojic acid are known as skin depigmenting agents.

On a cherché des substances qui présentent une action dépigmentante efficace, notamment supérieure à celle de l'arbutine et de l'acide kojique.Substances have been sought which exhibit an effective depigmenting action, in particular greater than that of arbutin and kojic acid.

Il subsiste le besoin d'un nouvel agent blanchissant de la peau humaine à action aussi efficace que ceux connus, mais n'ayant pas leurs inconvénients, c'est-à-dire qui soit non irritant, non toxique et/ou non allergisant pour la peau, tout en étant stable dans une composition, ou bien alternativement qui possède une action renforcée de façon à pouvoir être utilisé en quantité plus faible, ce qui diminue considérablement les effets secondaires observés.There remains a need for a novel whitening agent for human skin with an action as effective as those known, but not having their drawbacks, that is to say which is non-irritant, non-toxic and / or non-allergenic for the skin, while being stable in a composition, or alternatively which has an enhanced action so as to be able to be used in a smaller quantity, which considerably reduces the side effects observed.

A cet égard la Demanderesse a de manière surprenante et inattendue découvert que certains composés de résorcinol présentaient une bonne activité dépigmentante, même à faible concentration, sans faire preuve de cytotoxicité.In this regard, the Applicant has surprisingly and unexpectedly discovered that certain resorcinol compounds exhibit good depigmenting activity, even at low concentration, without showing cytotoxicity.

A cet égard, la Demanderesse a de manière surprenante et inattendue découvert que certains composés dérivés de résorcinol présentaient une bonne activité dépigmentante, même à faible concentration.In this regard, the Applicant has surprisingly and unexpectedly discovered that certain compounds derived from resorcinol exhibit good depigmenting activity, even at low concentration.

Certains composés dérivés de résorcinol sont déjà connus dans l'art antérieur pour leur activité dépigmentante. A cet égard on peut citer en particulier les documents JP 2007186445 de Kuraray .Certain compounds derived from resorcinol are already known in the prior art for their depigmenting activity. In this regard, we can cite in particular the documents JP 2007186445 from Kuraray .

L'invention a pour objet des composés de formule (I) tels que définis ci-après pour leur utilisation dermatologique pour dépigmenter la peau.The subject of the invention is compounds of formula (I) as defined below for their dermatological use for depigmenting the skin.

L'invention a également pour objet de nouveaux composés de formule (II) tels que définis ci-après.A subject of the invention is also new compounds of formula (II) as defined below.

L'invention a aussi pour objet un procédé de traitement cosmétique non thérapeutique de dépigmentation, d'éclaircissement et/ou de blanchiment des matières kératiniques, notamment de la peau, comprenant l'application sur la peau d'au moins un composé de formule (I) telle que définie ci-après.A subject of the invention is also a method of non-therapeutic cosmetic treatment for depigmentation, lightening and / or bleaching of keratin materials, in particular of the skin, comprising the application to the skin of at least one compound of formula ( I) as defined below.

L'invention a aussi pour objet une composition comprenant, dans un milieu physiologiquement acceptable, au moins un composé de formule (II) telle que définie ci-après.A subject of the invention is also a composition comprising, in a physiologically acceptable medium, at least one compound of formula (II) as defined below.

L'invention a également pour objet un procédé cosmétique non thérapeutique de dépigmentation, d'éclaircissement et/ou de blanchiment des matières kératiniques, notamment de la peau, comprenant l'application de la composition décrite précédemment.A subject of the invention is also a non-therapeutic cosmetic process for depigmentation, lightening and / or bleaching of keratin materials, in particular of the skin, comprising the application of the composition described above.

Plus préférablement, il s'agit du procédé pour dépigmenter, éclaircir et/ou blanchir la peau.More preferably, this is the method for depigmenting, lightening and / or whitening the skin.

L'invention concerne également l'utilisation cosmétique non thérapeutique d'au moins un composé de formule (I) telle que définie ci-après comme agent blanchissant, éclaircissant et/ou dépigmentant des matières kératiniques, notamment de la peau.The invention also relates to the non-therapeutic cosmetic use of at least one compound of formula (I) as defined below as an agent for whitening, lightening and / or depigmenting keratin materials, in particular the skin.

Les composés conformes à l'invention, à savoir en particulier de formule (I) ou de formule (II) telles que définies ci-après, permettent de dépigmenter et/ou d'éclaircir efficacement, voire de blanchir, la peau d'êtres humains. Ils sont notamment destinés à être appliqués sur la peau d'individus présentant des taches de pigmentation brunâtres, des taches de sénescence, ou sur la peau d'individus désirant combattre l'apparition d'une couleur brunâtre provenant de la mélanogénèse.The compounds in accordance with the invention, namely in particular of formula (I) or of formula (II) as defined below, make it possible to effectively depigment and / or lighten, or even whiten, the skin of human beings. humans. They are intended in particular to be applied to the skin of individuals exhibiting brownish pigmentation spots, spots of senescence, or to the skin of individuals wishing to combat the appearance of a brownish color originating from melanogenesis.

Ils peuvent également permettre de dépigmenter et/ou d'éclaircir les poils, les cils, les cheveux, ainsi que les lèvres et/ou les ongles.They can also make it possible to depigment and / or lighten the hairs, the eyelashes, the hair, as well as the lips and / or the nails.

L'invention a donc pour objet des composés de formule (I) comme suit, pour leur utilisation pour dépigmenter, éclaircir et/ou blanchir la peau :

Figure imgb0001
dans laquelle:

  • R1, R2 : identiques ou différents, désignent
    1. a) hydrogène,
    2. b) un radical COR5 dans lequel R5 désigne un radical alkyle linéaire en C1-C10 ou ramifié en C3-C10, de préférence un radical alkyle linéaire en C1-C6 ou ramifié en C3-C6, plus préférentiellement un radical alkyle linéaire en C1-C4
  • R3 désigne un radical alkyl linéaire en C1-C6 ou ramifié en C3-C6, de préférence un radical alkyle linéaire en C1-C4 ou ramifié en C3-C4,
  • R4 désigne
    1. a) H,
    2. b) un radical alkyl linéaire en C1-C6 ou ramifié en C3-C6,
    3. c) un radical COR5,
ainsi que leurs sels, leurs solvates et leurs isomères optiques, leurs racémiques, seuls ou en mélange.A subject of the invention is therefore compounds of formula (I) as follows, for their use for depigmenting, lightening and / or whitening the skin:
Figure imgb0001
 in which:
  • R 1 , R 2 : identical or different, denote
    1. a) hydrogen,
    2. b) a COR 5 radical in which R 5 denotes a linear C 1 -C 10 or branched C 3 -C 10 alkyl radical, preferably a linear C 1 -C 6 or branched C3-C6 alkyl radical, more preferably a linear C 1 -C 4 alkyl radical
  • R 3 denotes a linear C 1 -C 6 or branched C 3 -C 6 alkyl radical, preferably a linear C 1 -C 4 or branched C 3 -C 4 alkyl radical,
  • R 4 denotes
    1. a) H,
    2. b) a linear C 1 -C 6 or branched C 3 -C 6 alkyl radical,
    3. c) a COR 5 radical,
as well as their salts, their solvates and their optical isomers, their racemates, alone or as a mixture.

De préférence R1 et R2 sont identiques.Preferably R 1 and R 2 are identical.

De préférence R4 désigne H ou un radical alkyl linéaire en C1-C4, un radical alkyl ramifié en C3-C4 ou un radical COR5, plus préférentiellement H ou un radical COR5.Preferably R 4 denotes H or a linear C 1 -C 4 alkyl radical, a branched C 3 -C 4 alkyl radical or a COR 5 radical, more preferably H or a COR 5 radical.

Préférentiellement, les composés de formule (I) sont choisis parmi ceux pour lesquels :

  • R1, R2, identiques ou différents, désignent H ou un radical COCH3, et de préférence R1 et R2 sont identiques.
  • R3 désigne méthyle, éthyle ou isopropyle, et
  • R4 désigne H ou un radical COCH3.
ainsi que leurs sels, leurs solvates et leurs isomères optiques, leurs racémiques, seuls ou en mélange.Preferably, the compounds of formula (I) are chosen from those for which:
  • R 1 , R 2 , which are identical or different, denote H or a COCH 3 radical, and preferably R 1 and R 2 are identical.
  • R 3 denotes methyl, ethyl or isopropyl, and
  • R 4 denotes H or a COCH 3 radical.
as well as their salts, their solvates and their optical isomers, their racemates, alone or as a mixture.

Plus préférentiellement, les composés de formule (I) sont tels que :

  • R1, R2, identiques ou différents, désignent H ou un radical COCH3, et de préférence R1 et R2 sont identiques.
  • R3 désigne méthyle, et
  • R4 désigne H ou un radical COCH3,
ainsi que leurs sels, leurs solvates et leurs isomères optiques, leurs racémiques.More preferably, the compounds of formula (I) are such as:
  • R 1 , R 2 , which are identical or different, denote H or a COCH 3 radical, and preferably R 1 and R 2 are identical.
  • R 3 denotes methyl, and
  • R 4 denotes H or a COCH 3 radical,
as well as their salts, their solvates and their optical isomers, their racemates.

Toujours dans le cadre de la présente invention, les sels des composés de formule (I) telle que définie ci-après comprennent les sels non toxiques conventionnels desdits composés tels que ceux formés à partir d'acide ou de base.Still within the scope of the present invention, the salts of the compounds of formula (I) as defined below comprise the conventional non-toxic salts of said compounds such as those formed from acid or base.

Comme sels du composé de formule (I) on peut citer :

  • les sels obtenus par addition du composé de formule (I) (lorsqu'il comprend un groupe acide) avec une base minérale, telle que la soude, la potasse, l'hydroxyde de calcium, l'hydroxyde d'ammonium, l'hydroxyde de magnésium, l'hydroxyde de lithium, et les carbonates ou hydrogénocarbonates de sodium, de potassium ou de calcium par exemple ;
  • ou avec une base organique telle qu'une alkylamine primaire, secondaire ou tertiaire, par exemple la triéthylamine ou la butylamine. Cette alkylamine primaire, secondaire ou tertiaire peut comporter un ou plusieurs atomes d'azote et/ou d'oxygène et peut donc comporter par exemple une ou plusieurs fonctions alcool; on peut notamment citer l'amino-2-méthyl-2-propanol, l'éthanolamine, la triéthanolamine, la diméthylamino-2-propanol, le 2-amino-2-(hydroxyméthyl)-1,3-propanediol, la 3-(diméthylamino) propylamine.
As salts of the compound of formula (I), mention may be made of:
  • salts obtained by adding the compound of formula (I) (when it comprises an acid group) with an inorganic base, such as soda, potash, calcium hydroxide, ammonium hydroxide, hydroxide of magnesium, lithium hydroxide, and carbonates or hydrogen carbonates of sodium, potassium or calcium, for example;
  • or with an organic base such as a primary, secondary or tertiary alkylamine, for example triethylamine or butylamine. This primary, secondary or tertiary alkylamine can contain one or more nitrogen and / or oxygen atoms and can therefore contain, for example, one or more alcohol functions; mention may in particular be made of amino-2-methyl-2-propanol, ethanolamine, triethanolamine, dimethylamino-2-propanol, 2-amino-2- (hydroxymethyl) -1,3-propanediol, 3- (dimethylamino) propylamine.

On peut encore citer les sels d'acides aminés tels que par exemple, la lysine, l'arginine, la guanidine, l'acide glutamique, l'acide aspartique. Avantageusement, les sels des composés de formule (I) (lorsqu'il comprend un groupe acide) peuvent être choisis parmi les sels alcalins ou alcalinoterreux tels que sodium, potassium, calcium, magnésium ; les sels d'ammonium.Mention may also be made of salts of amino acids such as, for example, lysine, arginine, guanidine, glutamic acid or aspartic acid. Advantageously, the salts of the compounds of formula (I) (when it comprises an acid group) can be chosen from alkali or alkaline earth salts such as sodium, potassium, calcium, magnesium; ammonium salts.

Les solvates acceptables des composés décrits dans la présente invention comprennent des solvates conventionnels tels que ceux formés lors de la préparation desdits composés du fait de la présence de solvants. A titre d'exemple, on peut citer les solvates dus à la présence d'eau ou d'alcools linéaires ou ramifiés comme l'éthanol ou l'isopropanol.Acceptable solvates of the compounds described in the present invention include conventional solvates such as those formed during the preparation of said compounds due to the presence of solvents. By way of example, mention may be made of solvates due to the presence of water or of linear or branched alcohols such as ethanol or isopropanol.

Les isomères optiques sont notamment les énantiomères et les diastéréoismères.The optical isomers are in particular the enantiomers and the diastereoismers.

Toujours dans le cadre de la présente invention :
Sans indication contraire, un « groupe (Cx-Cy)alkyle » désigne un groupe alkyle linéaire et saturé comprenant de x à y atomes de carbone.Still within the scope of the present invention:
Without indication to the contrary, a “(C x -C y ) alkyl group” denotes a linear and saturated alkyl group comprising from x to y carbon atoms.

De façon préférentielle, les groupes alkyles linéaires saturés ou ramifiés peuvent être choisis parmi : méthyle, éthyle, propyle, isopropyle, butyle, isobutyle, tertio-butyle, pentyle, hexyle.Preferably, the saturated or branched linear alkyl groups can be chosen from: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl.

Les composés de formule (I) particulièrement préférés sont choisis parmi : Structure Composé n° Nom chimique

Figure imgb0002
1 4-(3-Hydroxy-1-méthyl-propyl)-benzène-1,3-diol
Figure imgb0003
 2 4-[4-(acétyloxy)butan-2-yl]benzène-1,3-diyl diacétate
Figure imgb0004
 3 3-(2,4-dihydroxyphényl)butyl acétate ainsi que leurs sels, leurs solvates et leurs isomères optiques, leurs racémiques, seuls ou en mélange.The particularly preferred compounds of formula (I) are chosen from: Structure Compound No. Chemical name
Figure imgb0002
 1 4- (3-Hydroxy-1-methyl-propyl) -benzene-1,3-diol
Figure imgb0003
 2 4- [4- (acetyloxy) butan-2-yl] benzene-1,3-diyl diacetate
Figure imgb0004
 3 3- (2,4-dihydroxyphenyl) butyl acetate as well as their salts, their solvates and their optical isomers, their racemates, alone or as a mixture.

Les composés de formule (I) sont nouveaux et constituent un autre objet de l'invention, ainsi que les compositions, en particulier les compositions cosmétiques, qui les contiennent ;The compounds of formula (I) are new and constitute another subject of the invention, as well as the compositions, in particular the cosmetic compositions, which contain them;

Les composés de l'invention de formule (I) peuvent être préparés selon le schéma 1 suivant.

Figure imgb0005
Figure imgb0006
 The compounds of the invention of formula (I) can be prepared according to scheme 1 below.
Figure imgb0005
Figure imgb0006

Selon ce schéma 1, la synthèse des composés (I) passe par l'intermédiaire clef de type dihydrocoumarine D dont la synthèse est entre autre décrite dans WO2005/085169 . L'homme de l'art peut en adapter la stratégie en fonction des groupements R3.According to this scheme 1, the synthesis of compounds (I) passes through the key intermediary of the dihydrocoumarin D type, the synthesis of which is among others described in WO2005 / 085169 . Those skilled in the art can adapt the strategy according to the R3 groups.

La résorcine A peut réagir en présence d'un beta céto-ester B pour conduire à la coumarine C. Cette dernière est réduite par une hydrogénation catalytique selon les conditions connues de l'homme du métier pour conduire à D.Resorcin A can react in the presence of a beta keto-ester B to lead to coumarin C. The latter is reduced by catalytic hydrogenation according to conditions known to those skilled in the art to lead to D.

D peut également être obtenu à partir de la résorcine A en présence d'un ester alpha beta insaturé E. La fonction lactonique de D est ensuite réduite par des hydrures, après d'éventuelles modifications préalables des fonctions phénoliques par des réactions connues de l'homme du métier telles que des réactions de protection/déprotection.D can also be obtained from resorcinol A in the presence of an alpha beta unsaturated ester E. The lactonic function of D is then reduced by hydrides, after possible prior modifications of the phenolic functions by known reactions of the those skilled in the art such as protection / deprotection reactions.

L'obtention des dérivés C et D via la réaction entre (A et B) ou (A et E) peut être réalisée notamment en présence d'un solvant organique pouvant être choisi parmi le toluène, le tétrahydrofurane, l'heptane, l'isooctane, le méthyltétrahydrofurane, la méthyléthyle cétone, la méthylisobutyle cétone, le dioxane, l'acétate d'éthyle, l'acétate d'isopropyle, l'isododécane et leurs mélanges, notamment à une température comprise entre 15 et 200 °C, éventuellement en présence d'un catalyseur (acide ou basique) tel que décrit dans les publications : Synthesis of 7-hydroxycoumarins by Pechmann reaction using Nafion resin/silica nanocomposites as catalysts : Laufer MC, Hausmann H, Hölderich WF, J of catalysis, 2003, 218, 315-320 ; Synthesis of 7-hydroxycoumarins catalysed by solid acid catalysts Hoefnagel A, Gunnewegh E, Downing R, van Bekkum H, J Chem Soc Chem Commun, 1995, 225-226 ; les dérivés C et D peuvent ainsi être obtenus en particulier en présence d'un catalyseur acide tel que l'acide sulfurique, l'acide méthanesulfonique, l'acide triflique, l'acide paratoluène sulfonique, des résines sulfoniques telles que les Dowex® ou les Amberlyst® (vendues par la société Aldrich).Obtaining the C and D derivatives via the reaction between (A and B) or (A and E) can be carried out in particular in the presence of an organic solvent which can be chosen from toluene, tetrahydrofuran, heptane, isooctane, methyltetrahydrofuran, methyl ethyl ketone, methyl isobutyl ketone, dioxane, ethyl acetate, isopropyl acetate, isododecane and their mixtures, in particular at a temperature between 15 and 200 ° C, optionally in the presence of a catalyst (acidic or basic) as described in the publications: Synthesis of 7-hydroxycoumarins by Pechmann reaction using Nafion resin / silica nanocomposites as catalysts: Laufer MC, Hausmann H, Hölderich WF, J of catalysis, 2003, 218, 315-320 ; Synthesis of 7-hydroxycoumarins catalysed by solid acid catalysts Hoefnagel A, Gunnewegh E, Downing R, van Bekkum H, J Chem Soc Chem Commun, 1995, 225-226 ; derivatives C and D can thus be obtained in particular in the presence of an acid catalyst such as sulfuric acid, methanesulphonic acid, triflic acid, paratoluenesulphonic acid, sulphonic resins such as Dowex® or Amberlyst® (sold by the company Aldrich).

Les composés de formule (I) pour lesquels R1 et ou R2 désignent un groupe COR5 peuvent être obtenus par acétylation/estérification. La réaction d'acétylation/estérification peut être effectuée avec l'anhydride acétique lorsque R5 désigne un radical méthyle (ou plus généralement un anhydride R5COOCOR5) ou le chlorure d'acétyle lorsque R5 désigne un radical méthyle (ou plus généralement un chlorure d'acide R5COCl), notamment en présence de solvant aprotique tel que le toluène, la pyridine, le tétrahydrofurane. La réaction d'acétylation/estérification peut être sélective en employant des groupements protecteurs sur les fonctions ne devant pas être acétylées/estérifiées et en effectuant après acétylation/esterification une réaction de déprotection, selon les techniques connues de la synthèse organique.The compounds of formula (I) for which R 1 and or R 2 denote a COR 5 group can be obtained by acetylation / esterification. The acetylation / esterification reaction can be carried out with acetic anhydride when R 5 denotes a methyl radical (or more generally an R 5 COOCOR 5 anhydride) or acetyl chloride when R 5 denotes a methyl radical (or more generally an acid chloride R5COCl), especially in the presence of an aprotic solvent such as toluene, pyridine, tetrahydrofuran. The acetylation / esterification reaction can be selective by employing protective groups on the functions which must not be acetylated / esterified and by carrying out, after acetylation / esterification, a deprotection reaction, according to known techniques of organic synthesis.

La réaction de réduction de la lactone D par des hydrures pour conduire au dérivé G peut être réalisée éventuellement en présence d'un solvant organique aprotique notamment le tétrahydrofurane, le dioxane, le diméthylformamide, le diméthylsulfoxyde, le 2-méthyltétrahydrofurane, le dichlorométhane , le toluène, à une température comprise entre 0 °C et 200 °C, notamment entre 20 °C et 60 °C.The reduction reaction of lactone D with hydrides to lead to derivative G can optionally be carried out in the presence of an aprotic organic solvent, in particular tetrahydrofuran, dioxane, dimethylformamide, dimethylsulfoxide, 2-methyltetrahydrofuran, dichloromethane, toluene, at a temperature between 0 ° C and 200 ° C, especially between 20 ° C and 60 ° C.

L'ensemble de ces étapes peuvent également faire appel à des stratégies de protection/déprotection usuellement utilisées en chimie organique et compilées dans l'ouvrage « Protecting Groups in Organic Synthesis » Greene, Wuts, Wiley Interscience , en fonction de la nature des radicaux, afin de placer sélectivement les groupements R1, R2 et/ou R4 tels que précédemment définis à partir du composé G.All of these steps can also call upon protection / deprotection strategies usually used in organic chemistry and compiled in the book. “Protecting Groups in Organic Synthesis” Greene, Wuts, Wiley Interscience , depending on the nature of the radicals, in order to selectively place the groups R1, R2 and / or R4 as defined above from the compound G.

A titre illustratif du schéma de synthèse général ci-dessus, on peut par exemple synthétiser les composés de formule (I) pour lesquels R1=R2=R4 = H et R3= méthyle, respectivement R3 = Ethyle) selon les schémas 2, ou 4 (respectivement selon le schéma 3) ci-dessous :
Dans ces schémas « t.a. » signifie température ambiante.

Figure imgb0007
Figure imgb0008
Figure imgb0009
 By way of illustration of the general synthetic scheme above, one can for example synthesize the compounds of formula (I) for which R1 = R2 = R4 = H and R3 = methyl, respectively R3 = Ethyl) according to schemes 2, or 4 (respectively according to diagram 3) below:
In these diagrams “ta” means room temperature.
Figure imgb0007
Figure imgb0008
Figure imgb0009

Selon le schéma 3, les réactifs, propionylacétate d'éthyle 5 et résorcinol réagissent comme décrit dans le schéma 1 ci-dessus pour donner le composé 6, qui peut être réduit par des hydrures pour conduire au composé de formule (I) correspondant. Une description de cette chimie peut être trouvée dans le document suivant Asian Journal of Chemistry, 2010, 22 (7), 5694-5698

Figure imgb0010
According to scheme 3, the reactants, ethyl propionylacetate 5 and resorcinol react as described in scheme 1 above to give compound 6, which can be reduced with hydrides to yield the corresponding compound of formula (I). A description of this chemistry can be found in the following document Asian Journal of Chemistry, 2010, 22 (7), 5694-5698
Figure imgb0010

Selon le schéma 4, on met à réagir du résorcinol avec de l'ester crotonique de méthyle en présence de MSOH en excès pour donner la 7-hydroxy-4-méthyl-3,4-dihydrocoumarine 2 qui après réduction par des hydrures, conduit au composé de formule (I) correspondant.According to scheme 4, resorcinol is reacted with crotonic methyl ester in the presence of excess MSOH to give 7-hydroxy-4-methyl-3,4-dihydrocoumarin 2 which after reduction with hydrides leads to the corresponding compound of formula (I).

Les composés de formule (I) selon l'invention trouvent une application toute particulière dans le domaine cosmétique.The compounds of formula (I) according to the invention find very particular application in the cosmetics field.

La composition selon l'invention comprend, dans un milieu physiologiquement acceptable, un composé de formule (I) tel que décrite précédemment.The composition according to the invention comprises, in a physiologically acceptable medium, a compound of formula (I) as described above.

Par milieu physiologiquement acceptable, on comprend un milieu compatible avec les matières kératiniques d'êtres humains comme la peau du corps ou du visage, les lèvres, les muqueuses, les cils, les ongles, le cuir chevelu et/ou les cheveux.By physiologically acceptable medium, one understands a medium compatible with the keratinous substances of human beings such as the skin of the body or of the face, the lips, the mucous membranes, the eyelashes, the nails, the scalp and / or the hair.

Le composé (I) peut être présent dans la composition selon l'invention en une quantité qui peut être comprise entre 0,01 et 10 % en poids, de préférence entre 0,1 à 5 % en poids, notamment de 0,5 à 3 % en poids, par rapport au poids total de la composition.The compound (I) can be present in the composition according to the invention in an amount which can be between 0.01 and 10% by weight, preferably between 0.1 to 5% by weight, in particular from 0.5 to 3% by weight, relative to the total weight of the composition.

La composition selon l'invention est avantageusement une composition cosmétique : elle peut comprendre des adjuvants usuellement employés dans le domaine cosmétique.The composition according to the invention is advantageously a cosmetic composition: it can comprise adjuvants usually used in the cosmetic field.

On peut notamment citer l'eau; les solvants organiques, notamment les alcools en C2-C6 ; les huiles, notamment les huiles hydrocarbonées, les huiles siliconées ; les cires, les pigments, les charges, les colorants, les tensioactifs, les émulsionnants ; les actifs cosmétiques, les filtres UV, les polymères, les épaississants, les conservateurs, les parfums, les bactéricides, les céramides, les absorbeurs d'odeur, les antioxydants.Mention may in particular be made of water; organic solvents, in particular C2-C6 alcohols; oils, in particular hydrocarbon-based oils, silicone oils; waxes, pigments, fillers, dyes, surfactants, emulsifiers; cosmetic active ingredients, UV filters, polymers, thickeners, preservatives, perfumes, bactericides, ceramides, odor absorbers, antioxidants.

Ces éventuels adjuvants cosmétiques peuvent être présents dans la composition à raison de 0,001 à 80 % en poids, notamment 0,1 à 40 % en poids, par rapport au poids total de la composition. En tout état de cause, ces adjuvants, ainsi que leurs proportions, seront choisis par l'homme du métier de manière telle que les propriétés avantageuses des composés selon l'invention ne soient pas, ou substantiellement pas, altérées par l'adjonction envisagée.These optional cosmetic adjuvants can be present in the composition in an amount of 0.001 to 80% by weight, in particular 0.1 to 40% by weight, relative to the total weight of the composition. In any event, these adjuvants, as well as their proportions, will be chosen by a person skilled in the art such that the advantageous properties of the compounds according to the invention are not, or not substantially, altered by the addition envisaged.

Comme actifs, il sera avantageux d'introduire dans la composition selon l'invention au moins un composé choisi parmi: les agents desquamants; les agents apaisants, les agents photoprotecteurs organique ou inorganique, les agents hydratants; les agents dépigmentants ; les agents anti-glycation; les inhibiteurs de NO-synthase; les agents stimulant la synthèse de macromolécules dermiques ou épidermiques et/ou empêchant leur dégradation; les agents stimulant la prolifération des fibroblastes et/ou des kératinocytes ou stimulant la différenciation des kératinocytes; les agents myorelaxants et/ou les agents dermo-décontractants; les agents tenseurs; les agents anti-pollution et/ou anti-radicalaire; les agents agissant sur la microcirculation; les agents agissant sur le métabolisme énergétique des cellules; et leurs mélanges.As active agents, it will be advantageous to introduce into the composition according to the invention at least one compound chosen from: desquamating agents; soothing agents, organic or inorganic photoprotective agents, moisturizing agents; depigmenting agents; anti-glycation agents; NO-synthase inhibitors; agents stimulating the synthesis of dermal or epidermal macromolecules and / or preventing their degradation; agents stimulating the proliferation of fibroblasts and / or keratinocytes or stimulating the differentiation of keratinocytes; muscle relaxants and / or dermo-relaxants; tensioning agents; anti-pollution and / or anti-radical agents; agents acting on the microcirculation; agents acting on the energy metabolism of cells; and their mixtures.

La composition selon l'invention peut se présenter sous toutes les formes galéniques normalement utilisées dans le domaine cosmétique, et notamment sous forme d'une solution aqueuse ou hydroalcoolique, éventuellement gélifiée, d'une dispersion du type lotion éventuellement biphasée, d'une émulsion huile-dans-eau ou eau-dans-huile ou multiple ((E/H/E ou H/E/H par exemple), d'un gel aqueux, d'une dispersion d'huile dans une phase aqueuse à l'aide de sphérules, ces sphérules pouvant être des nanoparticules polymériques telles que les nanosphères et les nanocapsules ou, mieux, des vésicules lipidiques de type ionique et/ou non ionique; de gel aqueux ou huileux. Ces compositions sont préparées selon les méthodes usuelles. On préfère utiliser selon cette invention une composition sous la forme d'une émulsion notamment huile-dans-eau.The composition according to the invention can be provided in all the galenic forms normally used in the cosmetics field, and in particular in the form of an aqueous or hydroalcoholic solution, optionally gelled, of an optionally two-phase lotion-type dispersion, of an emulsion. oil-in-water or water-in-oil or multiple ((W / O / W or O / W / O for example), of an aqueous gel, of an oil dispersion in an aqueous phase to the using spherules, these spherules possibly being polymeric nanoparticles such as nanospheres and nanocapsules or, better, lipid vesicles of ionic and / or nonionic type, of aqueous or oily gel. These compositions are prepared according to the usual methods. prefers to use according to this invention a composition in the form of an emulsion in particular oil-in-water.

La composition selon l'invention peut constituer une composition de soin de la peau, et notamment une crème de nettoyage, de protection, de traitement ou de soin pour le visage, pour les mains, pour les pieds, pour les grands plis anatomiques ou pour le corps (par exemple crèmes de jour, crèmes de nuit, crèmes démaquillantes, crèmes de fond de teint, crèmes anti-solaires); un fond de teint fluide, un lait de démaquillage, un lait corporel de protection ou de soin, un lait anti-solaire; une lotion, gel ou mousse pour le soin de la peau, comme une lotion de nettoyage.]The composition according to the invention can constitute a skin care composition, and in particular a cream for cleaning, protecting, treating or caring for the face, for the hands, for the feet, for the large anatomical folds or for the body (eg day creams, night creams, makeup removing creams, foundation creams, sunscreen creams); a fluid foundation, a cleansing milk, a protective or care body milk, an anti-sun milk; a skin care lotion, gel or foam, such as a cleansing lotion.]

L'invention est illustrée plus en détail par les exemples non limitatifs suivants.The invention is illustrated in more detail by the following non-limiting examples.

Exemple 1 : synthèse du composé 1 : Example 1 : synthesis of compound 1:

Figure imgb0011
Figure imgb0011

Réactifs :Reagents:

  • 7-HYDROXY-4-METHYL-3,4-DIHYDRO-2H-1-BENZOPYRAN-2-ONE : 5.7 g7-HYDROXY-4-METHYL-3,4-DIHYDRO-2H-1-BENZOPYRAN-2-ONE: 5.7 g
  • LiAIH4 poudre (3 eq) : 3.7 gLiAIH4 powder (3 eq): 3.7 g
  • THF anhydre : 250 mlAnhydrous THF: 250 ml
Mode opératoire :Procedure:

Dans un ballon, on a introduit le LiAlH4, le THF (en partie), puis goutte à goutte la coumarine en solution. On a laissé sous agitation une nuit à Température ambiante.LiAlH4, THF (in part), then coumarin in solution drop by drop were introduced into a flask. Stirring was left overnight at room temperature.

On a refroidit le milieu réactionnel à 0°C et on a ajouté avec précaution 20 ml d'eau puis 250 ml d'HCl 1 N. Le THF a été évaporé , puis le résidu a été extrait 3 fois à l'éther diéthylique. Les phases organiques réunies ont été lavées avec une solution de NaCl saturé, puis séchées avec Na2SO4, filtrées et évaporées.The reaction medium was cooled to 0 ° C. and 20 ml of water and then 250 ml of 1N HCl were carefully added. The THF was evaporated off, then the residue was extracted 3 times with diethyl ether. The combined organic phases were washed with saturated NaCl solution, then dried with Na2SO4, filtered and evaporated.

On a récupéré 5 g d'une poudre légèrement rosée correspondant au composé attendu (rendement 86 %).5 g of a slightly pink powder corresponding to the expected compound were recovered (yield 86%).

Les spectres RMN 1H et de masse sont conformes à la structure.
Point de fusion : 128.8-129.4°C (tube capillaire)The 1H NMR and mass spectra are consistent with the structure.
Melting point: 128.8-129.4 ° C (capillary tube)

Exemple 2 : synthèse du composé 2 : Example 2 : synthesis of compound 2:

Figure imgb0012
Figure imgb0012

Réactifs :Reagents:

  • 4-(4-hydroxybutan-2-yl)benzene-1,3-diol : 0.8 g4- (4-hydroxybutan-2-yl) benzene-1,3-diol: 0.8 g
  • Anhydride acétique (3 eq) : 1.2 mlAcetic anhydride (3 eq): 1.2 ml
  • Pyridine : 5 mlPyridine: 5 ml
Mode opératoire : Procedure :

Dans un ballon, on a introduit le 4-(4-hydroxybutan-2-yl)benzène-1,3-diol, puis la pyridine. On a refroidit le milieu à 0°C et puis on a ajouté l'anhydride acétique. On a laissé sous agitation une nuit à température ambiante.In a flask, 4- (4-hydroxybutan-2-yl) benzene-1,3-diol was introduced, followed by pyridine. The medium was cooled to 0 ° C and then acetic anhydride was added. Stirring was left overnight at room temperature.

On a ajouté 50 ml d'acétate d'éthyle et 50 ml HCl 1 N. On a lavé la phase organique avec 2 fois 50 ml HCl 1 N , puis 50 ml d'eau et 50 ml d'une solution saturée de NaCl. La phase organique a été séchée avec Na2SO4, filtrée et évaporée.50 ml of ethyl acetate and 50 ml of 1 N HCl were added. The organic phase was washed with 2 times 50 ml of 1 N HCl, then 50 ml of water and 50 ml of a saturated solution of NaCl. The organic phase was dried with Na2SO4, filtered and evaporated.

On a récupéré 1 g d'une huile jaune correspondant au composé attendu. (rendement 77 %).1 g of a yellow oil corresponding to the expected compound was recovered. (yield 77%).

Les spectres RMN 1H et de masse sont conformes à la structure.The 1H NMR and mass spectra are consistent with the structure.

Exemple 3 : synthèse du composé 3 : Example 3 : synthesis of compound 3:

Figure imgb0013
Figure imgb0013

Réactifs :Reagents:

  • 4-[4-(acétyloxy)butan-2-yl]benzène-1,3-diyl diacétate : 0.4 g4- [4- (acetyloxy) butan-2-yl] benzene-1,3-diyl diacetate: 0.4 g
  • Hydrogénocarbonate de potassium (2 eq) : 260 mgPotassium hydrogen carbonate (2 eq): 260 mg
  • Eau : 1 mlWater: 1 ml
  • Ethanol : 2 mlEthanol: 2 ml
Mode opératoire :Procedure:

Dans un ballon, on a introduit le 4-[4-(acétyloxy)butan-2-yl]benzene-1,3-diyl diacétate et l'éthanol, puis on a ajouté l'eau et le KHCO3.In a flask, 4- [4- (acetyloxy) butan-2-yl] benzene-1,3-diyl diacetate and ethanol were added, then water and KHCO3 were added.

On a laissé 1h à température ambiante. On a évaporé l'éthanol et on a extrait à l'acétate d'éthyle. La phase organique a été séchée avec Na2SO4, puis filtrée et évaporée.It was left for 1 hour at room temperature. Ethanol was evaporated and extracted with ethyl acetate. The organic phase was dried with Na2SO4, then filtered and evaporated.

On a récupéré 0, 25 g d'une huile jaune correspondant au composé attendu . (rendement 86 %).0.25 g of a yellow oil corresponding to the expected compound was recovered. (yield 86%).

Les spectres RMN 1H et de masse sont conformes à la structure attendue.The 1H NMR and mass spectra are in accordance with the expected structure.

Exemple 4 : Mise en évidence de l'activité sur la mélanogénèse constitutiveExample 4: Demonstration of the activity on constitutive melanogenesis

L'efficacité a été démontrée sur la base du test suivant :
Les évaluations de l'effet de prévention ou de diminution de la pigmentation de la peau et / ou de l'éclaircissement de celle-ci peau les exemples sont réalisés de la manière suivante.Efficacy has been demonstrated on the basis of the following test:
The evaluations of the effect of preventing or reducing the pigmentation of the skin and / or of the lightening of the latter, the examples are carried out as follows.

La mesure de l'activité dépigmentante (réduction de la production de mélanine) de composés de formule (I) a été effectuée par dosage des mélanocytes humains normaux in vitro comme suit.The measurement of the depigmenting activity (reduction of melanin production) of compounds of formula (I) was carried out by assaying normal human melanocytes in vitro as follows.

Tout d'abord, des mélanocytes humains normaux sont cultivés et distribués dans 384puits. Après 24 heures, le milieu de culture a été remplacé par un milieu contenant des composés de formule (I) à évaluer. Les cellules ont été incubées 72 heures avant la mesure de la densité optique finale qui mesure la quantité de mélanine produite par les mélanocytes. Un effet dose est mis en œuvre en utilisant une large gamme de concentration des composés évalués. Ainsi, en faisant correspondre les concentrations et les mesures de mélanine, il est possible de déterminer une CI50 en µM: concentration à laquelle 50 % de diminution de la synthèse de mélanine est atteinte.First, normal human melanocytes are cultured and distributed in 384 wells. After 24 hours, the culture medium was replaced by a medium containing compounds of formula (I) to be evaluated. The cells were incubated 72 hours before the measurement of the final optical density which measures the amount of melanin produced by melanocytes. A dose effect is implemented by using a wide range of concentrations of the compounds evaluated. Thus, by matching the concentrations and measurements of melanin, it is possible to determine an IC50 in μM: concentration at which 50% reduction in melanin synthesis is reached.

Les composés de formule (I) ont montré un effet dépigmentant fort. N° Composé IC50 (µM) Concentration maximale testée (µM) 1 3,61 200 2 4,08 200 3 4,96 200 The compounds of formula (I) have shown a strong depigmenting effect. Compound No. IC50 (µM) Maximum concentration tested (µM) 1 3.61 200 2 4.08 200 3 4.96 200

Ces résultats ont été comparés à ceux obtenus avec le composé le plus proche décrit dans l'art antérieur, dans le brevet JP 2007186445 de Kuraray

Figure imgb0014
These results were compared with those obtained with the closest compound described in the prior art, in the patent JP 2007186445 from Kuraray
Figure imgb0014

Pour ce composé (A), la valeur de l'IC50 est de 23,4 µM concentration maximale testée 200µM.For this compound (A), the value of the IC50 is 23.4 μM maximum concentration tested 200 μM.

Les composés de l'invention ont une activité sur la réduction de la mélanogénèse beaucoup plus importante que celle du composé (A) hors invention ;The compounds of the invention have an activity on the reduction of melanogenesis much greater than that of compound (A) outside the invention;

Exemple 5 : Composition cosmétiqueExample 5: Cosmetic composition

On prépare une composition dépigmentante pour la peau comprenant (en gramme) : Composé n°1 2 g PEG400 68 g Ethanol 30 g A depigmenting composition for the skin is prepared comprising (in grams): Compound # 1 2 g PEG400 68 g Ethanol 30 g

La composition appliquée sur la peau permet d'estomper les taches brunes.The composition applied to the skin helps to reduce dark spots.

Exemple 6 : gelExample 6: gel

On prépare un gel dépigmentant pour la peau comprenant (% en poids) : Composé n°2 0,25% Carbomer (Carbopol 981 de chez Lubrizol) 1% conservateur qs eau qsp 100 % A depigmenting gel for the skin is prepared comprising (% by weight): Compound # 2 0.25% Carbomer (Carbopol 981 from Lubrizol) 1% conservative qs water qsp 100%

La composition appliquée sur la peau permet d'estomper les taches brunes.The composition applied to the skin helps to reduce dark spots.

Exemple 7 : Mise en évidence de l'activité dépigmentante sur un épiderme reconstruit pigmentéExample 7: Demonstration of the depigmenting activity on a reconstructed pigmented epidermis

Le but de ce test est d'évaluer la modulation de la mélanogénèse dans les épidermes reconstruits pigmentés après application « systémique » des produits.

  • Les composés sont testés à 30µM dans le DMSO.
  • Les épidermes pigmentés sont reconstruits à l'aide de kératinocytes et mélanocytes d'origine européenne ensemencés sur le substrat BPER (EPISKIN). Les produits à tester sont ajoutés au milieu de culture dès l'ensemencement des cellules et à tous les changements de milieu.
The aim of this test is to evaluate the modulation of melanogenesis in reconstructed pigmented epidermis after “systemic” application of the products.
  • The compounds are tested at 30 μM in DMSO.
  • The pigmented epidermis are reconstructed using keratinocytes and melanocytes of European origin seeded on the BPER substrate (EPISKIN). The products to be tested are added to the culture medium as soon as the cells are inoculated and whenever the medium changes.

Le modèle d'étude type épiderme reconstruit pigmenté a été publié par :
Regnier M, Duval C, Galey JB, Philippe M, Lagrange A, Tuloup R, Schmidt R, Cellular and Molecular Biology, 1999, 45, 7, 969-980 : « Keratinocyte-Melanocyte co-cultures and pigmented reconstructed human epidermis : models to study modulation of melanogenesis » .The pigmented reconstructed epidermis type study model was published by:
Regnier M, Duval C, Galey JB, Philippe M, Lagrange A, Tuloup R, Schmidt R, Cellular and Molecular Biology, 1999, 45, 7, 969-980: “Keratinocyte-Melanocyte co-cultures and pigmented reconstructed human epidermis: models to study modulation of melanogenesis " .

La mélanine a été quantifiée par analyse d'images sur coupes histologiques après révélation par coloration Fontana Masson. Chaque épiderme coloré est photographié sur toute sa longueur à l'aide d'une caméra reliée à un microscope.The melanin was quantified by analysis of images on histological sections after revelation by Fontana Masson staining. Each colored epidermis is photographed along its entire length using a camera connected to a microscope.

Les résultats sont rassemblés dans le tableau suivant :
La diminution de la quantité de mélanine est évaluée par rapport au solvant (DMSO) Activité dépigmentante/DMSO Lucinol -41% Composé 1 -59% The results are collated in the following table:
The decrease in the amount of melanin is evaluated relative to the solvent (DMSO) Depigmenting activity / DMSO Lucinol -41% Compound 1 -59%

Les résultats obtenus montrent que le composé 1 selon l'invention a une action dépigmentante plus importante que celle du lucinol.The results obtained show that compound 1 according to the invention has a greater depigmenting action than that of lucinol.

Claims (13)

  1. Non-therapeutic cosmetic use of at least one compound of formula (I) as an agent for bleaching, lightening and/or depigmenting keratin materials, especially the skin:
    Figure imgb0031
     in which:
    R1 and R2, which may be identical or different, denote:
    a) hydrogen,
    b) a COR5 radical in which R5 denotes a linear C1-C10 or branched C3-C10 alkyl radical, preferably a linear C1-C6 or branched C3-C6 alkyl radical, more preferentially a linear C1-C4 alkyl radical,
    R3 denotes a linear C1-C6 or branched C3-C6 alkyl radical, preferably a linear C1-C4 or branched C3-C4 alkyl radical,
    R4 denotes
    a) H,
    b) a linear C1-C6 or branched C3-C6 alkyl radical,
    c) a COR5 radical,
    and also the salts thereof, the solvates thereof and the optical isomers thereof, and the racemates thereof, alone or as a mixture.
  2. Use according to Claim 1, characterized in that R4 denotes H or a linear C1-C4 alkyl radical, a branched C3-C4 alkyl radical or a COR5 radical, more preferentially H or a COR5 radical.
  3. Use according to either of Claims 1 and 2, characterized in that the compounds of formula (I) are chosen from those for which:
    R1 and R2, which may be identical or different, denote H or a COCH3 radical, and preferably R1 and R2 are identical,
    R3 denotes methyl, ethyl or isopropyl, and
    R4 denotes H or a COCH3 radical,
    and also the salts thereof, the solvates thereof and the optical isomers thereof, and the racemates thereof, alone or as a mixture.
  4. Use according to one of Claims 1 to 3, characterized in that the compounds of formula (I) are chosen from those for which:
    R1 and R2, which may be identical or different, denote H or a COCH3 radical, and preferably R1 and R2 are identical,
    R3 denotes methyl, and
    R4 denotes H or a COCH3 radical,
    and also the salts thereof, the solvates thereof and the optical isomers thereof, and the racemates thereof.
  5. Use according to one of Claims 1 to 4, characterized in that the compounds of formula (I) are chosen from: Structure Compound No. Chemical name
    Figure imgb0032
         1 4-(3-hydroxy-1-methylpropyl) benzene-1,3-diol
    Figure imgb0033
         2 4-[4-(acetyloxy)but-2-yl]benzene-1,3-diyl diacetate
    Figure imgb0034
         3 3-(2,4-dihydroxyphenyl) butyl acetate
    and also the salts thereof, the solvates thereof and the optical isomers thereof, and the racemates thereof, alone or as a mixture.
  6. Compounds of formula (I) below:
    Figure imgb0035
     in which:
    R1 and R2, which may be identical or different, denote:
    a) hydrogen,
    b) a COR5 radical in which R5 denotes a linear C1-C10 or branched C3-C10 alkyl radical, preferably a linear C1-C6 or branched C3-C6 alkyl radical, more preferentially a linear C1-C4 alkyl radical,
    R3 denotes a linear C1-C6 or branched C3-C6 alkyl radical, preferably a linear C1-C4 or branched C3-C4 alkyl radical,
    R4 denotes
    a) H,
    b) a linear C1-C6 or branched C3-C6 alkyl radical,
    c) a COR5 radical in which R5 denotes a linear C1-C10 or branched C3-C10 alkyl radical, preferably a linear C1-C6 or branched C3-C6 alkyl radical, more preferentially a linear C1-C4 alkyl radical,
    and also the salts thereof, the solvates thereof and the optical isomers thereof, and the racemates thereof, alone or as a mixture.
  7. Compound of formula (I) according to Claim 6, characterized in that R4 denotes H or a linear C1-C4 alkyl radical, a branched C3-C4 alkyl radical or a COR5 radical, more preferentially H or a COR5 radical.
  8. Compound of formula (I) according to either of Claims 6 and 7, characterized in that:
    R1 and R2, which may be identical or different, denote H or a COCH3 radical, and preferably R1 and R2 are identical,
    R3 denotes methyl, ethyl or isopropyl, and
    R4 denotes H or a COCH3 radical,
    and also the salts thereof, the solvates thereof and the optical isomers thereof, and the racemates thereof, alone or as a mixture.
  9. Compound of formula (I) according to one of claims 6 to 8, characterized in that:
    R1 and R2, which may be identical or different, denote H or a COCH3 radical, and preferably R1 and R2 are identical,
    R3 denotes methyl, and
    R4 denotes H or a COCH3 radical,
    and also the salts thereof, the solvates thereof and the optical isomers thereof, and the racemates thereof.
  10. Compound of formula (I) according to one of claims 6 to 9, characterized in that the compounds of formula (I) are chosen from: Structure Compound No. Chemical name
    Figure imgb0036
         1 4-(3-hydroxy-1-methylpropyl)benzene-1,3-diol
    Figure imgb0037
         2 4-[4-(acetyloxy)but-2-yl]benzene-1,3-diyl diacetate
    Figure imgb0038
         3 3-(2,4-dihydroxyphenyl) butyl acetate
    and also the salts thereof, the solvates thereof and the optical isomers thereof, and the racemates thereof, alone or as a mixture.
  11. Composition comprising, in a physiologically acceptable medium, at least one compound of formula (I) according to any one of Claims 6 to 10.
  12. Composition according to the preceding claim, characterized in that said compound of formula (I) is present in an amount of between 0.01% and 10% by weight, preferably between 0.1% and 5% by weight and in particular from 0.5% to 3% by weight, relative to the total weight of the composition.
  13. Non-therapeutic cosmetic process for depigmenting, lightening and/or bleaching keratin materials, especially the skin, comprising the application of the composition according to Claim 11 or 12.
EP16815770.9A 2015-12-16 2016-12-08 Resorcinol derivatives for cosmetic use thereof Active EP3390343B1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR1562542A FR3045600B1 (en) 2015-12-16 2015-12-16 RESORCINOL DERIVATIVES FOR THEIR COSMETIC USE
PCT/EP2016/080237 WO2017102536A1 (en) 2015-12-16 2016-12-08 Resorcinol derivatives for cosmetic use thereof

Publications (2)

Publication Number Publication Date
EP3390343A1 EP3390343A1 (en) 2018-10-24
EP3390343B1 true EP3390343B1 (en) 2020-10-14

Family

ID=55862893

Family Applications (1)

Application Number Title Priority Date Filing Date
EP16815770.9A Active EP3390343B1 (en) 2015-12-16 2016-12-08 Resorcinol derivatives for cosmetic use thereof

Country Status (6)

Country Link
US (1) US10457619B2 (en)
EP (1) EP3390343B1 (en)
CN (1) CN108368026B (en)
ES (1) ES2843728T3 (en)
FR (1) FR3045600B1 (en)
WO (1) WO2017102536A1 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR3067027B1 (en) * 2017-05-31 2019-06-21 L'oreal RESORCINOL DERIVATIVES FOR THEIR COSMETIC USE
FR3068353B1 (en) * 2017-06-30 2020-05-08 L'oreal RESORCINOL DERIVATIVES FOR THEIR COSMETIC USE
US20220280405A1 (en) * 2019-08-28 2022-09-08 Conopco, Inc. , d/b/a UNILEVER Novel compounds for skin lightening

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7300646B2 (en) * 2004-02-27 2007-11-27 Unilever Home & Personal Care Usa, Division Of Conopco, Inc. Skin lightening agents, compositions and methods
US20060210497A1 (en) * 2005-03-18 2006-09-21 Unilever Home & Personal Care Usa, Division Of Conopco, Inc. Novel resorcinol derivatives
JP4986110B2 (en) * 2006-01-12 2012-07-25 国立大学法人九州大学 Melanin production inhibitor containing resorcinol derivative
DE102007038097A1 (en) * 2007-08-13 2009-02-19 Merck Patent Gmbh tyrosinase
CN102099001A (en) * 2008-07-21 2011-06-15 尤尼根公司 Series of skin-whitening (lightening) compounds
FR2971249B1 (en) * 2011-02-07 2013-10-18 Fabre Pierre Dermo Cosmetique HETEROCYCLIC DERIVATIVES OF RESORCINOL, THEIR PREPARATION AND THEIR COSMETIC USES

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

Also Published As

Publication number Publication date
FR3045600A1 (en) 2017-06-23
CN108368026B (en) 2021-10-22
WO2017102536A1 (en) 2017-06-22
EP3390343A1 (en) 2018-10-24
ES2843728T3 (en) 2021-07-20
US20180370886A1 (en) 2018-12-27
US10457619B2 (en) 2019-10-29
CN108368026A (en) 2018-08-03
FR3045600B1 (en) 2018-01-26

Similar Documents

Publication Publication Date Title
EP0820767B2 (en) Use of melatonin derivatives for skin depigmentation and compositions comprising the same
EP0966434B1 (en) Aminophenol derivatives and their use in cosmetics
FR3045604A1 (en) PROCESS FOR DEPIGMENTING KERATINIC MATERIALS USING THIOPYRIDINONE COMPOUNDS
EP1001741A1 (en) Use of amino phenol amide derivatives as depigmentation agents
FR2843963A1 (en) New 1,2,9,10-tetraoxy-noraporphine derivatives, useful in cosmetic or dermatological compositions having e.g. pigmentation reducing, antiaging and slimming action
FR2968661A1 (en) PROCESS FOR DEPIGMENTING KERATINIC MATERIALS USING THIOPYRIDINONE COMPOUNDS
EP3390343B1 (en) Resorcinol derivatives for cosmetic use thereof
FR2767689A1 (en) USE OF OXAMATE DERIVATIVES AS DEPIGMENTING AGENTS
FR2991985B1 (en) PROCESS FOR DEPIGMENTING KERATINIC MATERIALS USING NOVEL RESORCINOL DERIVED COMPOUNDS
EP1878470B1 (en) Skin depigmentation method
EP0819692B1 (en) Kojic acid derivative as depigmentation agent
EP0820763A2 (en) Use of N,N'-dibenzyl-ethylene diamine acid derivatives as depigmentation agents
FR3067027B1 (en) RESORCINOL DERIVATIVES FOR THEIR COSMETIC USE
FR3045039A1 (en) RESORCINOL DERIVATIVES FOR THEIR COSMETIC USE
WO2008129188A1 (en) Method for the depigmentation of keratinous materials with the help of carbamate compounds of vitamin c, and use of said compounds
FR2886844A1 (en) Use of 2-oxyacetamide compounds for promoting, inducing and/or stimulating the pigmentation of human keratin materials, preventing and/or limiting the depigmentation, and/or bleaching of keratin materials
WO2005121067A1 (en) Composition, particularly a cosmetic composition, comprising ((dialkylamino)alkoxy) ethanol ester
FR3071731A1 (en) RESORCINOL DERIVATIVES FOR THEIR COSMETIC USE
FR2991986A1 (en) NOVEL RESORCINOL DERIVATIVES AND THEIR COSMETIC APPLICATIONS
EP2935231B1 (en) C-xyloside compounds, compositions and use thereof to depigment the skin
EP1738741A2 (en) Use of benzylidene-1,3-thiazolidine-2,4-diones for favouring and/or inducing and/or stimulating the pigmentation of keratinic materials and/or for limiting their depigmentation and/or their bleaching
FR3068353A1 (en) RESORCINOL DERIVATIVES FOR THEIR COSMETIC USE
FR3066492A1 (en) RESORCINOL DERIVATIVES FOR THEIR COSMETIC USE
EP1774958A1 (en) Use of phenylfurylmethylthiazolidine-2,4-dione or phenylthienylmethylthiazolidine-2,4-dione compounds for promoting and/or inducing and/or stimulating the pigmentation of keratinous substances and/or limiting their depigmentation and/or their whitening
FR3097435A1 (en) Xyloside derivatives of resveratrol for their use in cosmetics

Legal Events

Date Code Title Description
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: UNKNOWN

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE

PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20180716

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME

DAV Request for validation of the european patent (deleted)
DAX Request for extension of the european patent (deleted)
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: EXAMINATION IS IN PROGRESS

17Q First examination report despatched

Effective date: 20190718

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: GRANT OF PATENT IS INTENDED

INTG Intention to grant announced

Effective date: 20200604

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE PATENT HAS BEEN GRANTED

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

Free format text: NOT ENGLISH

REG Reference to a national code

Ref country code: AT

Ref legal event code: REF

Ref document number: 1323426

Country of ref document: AT

Kind code of ref document: T

Effective date: 20201015

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 602016045946

Country of ref document: DE

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

Free format text: LANGUAGE OF EP DOCUMENT: FRENCH

REG Reference to a national code

Ref country code: AT

Ref legal event code: MK05

Ref document number: 1323426

Country of ref document: AT

Kind code of ref document: T

Effective date: 20201014

REG Reference to a national code

Ref country code: NL

Ref legal event code: MP

Effective date: 20201014

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: RS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210215

Ref country code: NO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210114

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210115

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

REG Reference to a national code

Ref country code: LT

Ref legal event code: MG4D

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

Ref country code: AT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210114

Ref country code: LV

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210214

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

Ref country code: HR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 602016045946

Country of ref document: DE

REG Reference to a national code

Ref country code: ES

Ref legal event code: FG2A

Ref document number: 2843728

Country of ref document: ES

Kind code of ref document: T3

Effective date: 20210720

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SM

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

Ref country code: LT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

Ref country code: MC

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

REG Reference to a national code

Ref country code: BE

Ref legal event code: MM

Effective date: 20201231

26N No opposition filed

Effective date: 20210715

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20201208

Ref country code: AL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20201208

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20201231

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20201231

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: IT

Payment date: 20211110

Year of fee payment: 6

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210214

Ref country code: TR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

Ref country code: MT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: ES

Payment date: 20220105

Year of fee payment: 6

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20201014

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20201231

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 20230929

Year of fee payment: 8

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20231019

Year of fee payment: 8

REG Reference to a national code

Ref country code: ES

Ref legal event code: FD2A

Effective date: 20240126

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20221208

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 20231010

Year of fee payment: 8

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: ES

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20221209

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: ES

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20221209